Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. METHODS: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. CONCLUSION: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

The association between retinol-binding protein 4 and prediabetes in obese patients with nonalcoholic fatty liver disease.

CONTEXT: Retinol-binding protein 4 (RBP4) is associated with visceral fat and insulin resistance (IR) in obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), but some of these data remain controversial. OBJECTIVE: This study evaluated the relationship between serum RBP4 levels and prediabetes in obese patients with NAFLD. METHODS: A total of 79 obese NAFLD patients without (n = 41) and with prediabetes (n = 38) were included. Serum RBP4 was measured using ELISA method. RESULTS: Higher RBP4 serum levels were observed in patients with prediabetes, metabolic syndrome (MetS), or dyslipidaemia. There was correlation between RBP4 levels and visceral adiposity index (VAI), glucose, insulin, HOMA-IR, and Quicki index. RBP4 ≥ 61 mcg/ml have about 3.5-fold higher risk of prediabetes (OR 3.544, 95% CI 1.385-9.072, p=.008), and RBP4 ≥ 55 mcg/ml increased the risk for MetS approximately 3.1 times. CONCLUSIONS: RBP4 is associated with increased risk for prediabetes and MetS in obese patients with NAFLD.

Increased Serum Pentraxin 3 Is Associated with Prediabetes and Type 2 Diabetes in Obese Patients with Nonalcoholic Fatty Liver Disease.

Background: Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Results: Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL, P = 0.028). There were significant correlations between PTX3 and alanine aminotransferase (P = 0.018), gamma-glutamyl transferase (P = 0.005), and neuropathy disability score (P < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. Conclusions: PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.

Lumican in Obese Patients with Nonalcoholic Fatty Liver Disease With or Without Prediabetes.

Background: Lumican is a small leucine-rich proteoglycan that regulates the assembly of collagen fibers in the extracellular matrix of different tissues. Excess collagen production in the liver is key in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and might contribute to the risk of type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to evaluate the relationship between serum lumican and prediabetes, and other biochemical and clinical parameters in obese subjects with NAFLD. Methods: The study group included 79 subjects with obesity and NAFLD of which 41 had normal carbohydrate tolerance and 38 had prediabetes. Serum lumican was measured by means of enzyme-linked immunosorbent assay. Results: Higher lumican serum levels were found in patients with prediabetes compared with those with normal carbohydrate tolerance (0.117 ± 0.074 vs. 0.080 ± 0.048 ng/mL, P = 0.010) as well as in subjects with metabolic syndrome (MetS) versus those without MetS (0.113 ± 0.071 vs. 0.079 ± 0.048 ng/mL, P = 0.034). There was also a modest positive association between lumican levels and fasting glucose (r = 0.228, P < 0.05). Lumican levels ≥0.07 ng/mL determine a 3.9-fold higher risk of prediabetes (odds ratio: 3.945, 95% confidence interval: 1.518-10.254, P = 0.005). Conclusions: Lumican levels were higher in obese subjects with NAFLD with prediabetes and MetS. Lumican bears an increased risk for prediabetes in the study population.

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. METHODS: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.